@article{a383fe82b0334d9cb27490f5f823674e,
title = "Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis",
abstract = "How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes uridine 5′-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3), drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering.",
keywords = "actomyosin, cadherin, ECM, hyaluronan, hyaluronic acid, hydraulics, inner ear, semicircular canals, tissue morphogenesis, zebrafish",
author = "Akankshi Munjal and Edouard Hannezo and Tsai, {Tony Y.C.} and Mitchison, {Timothy J.} and Megason, {Sean G.}",
note = "Funding Information: We thank Ian Swinburne, Sandy Nandagopal, and Toru Kawanishi for support, discussions, and reagents. We thank Vanessa Barone, Joseph Nasser, and members of the Megason lab for useful comments on the manuscript and general feedback. We are grateful to the Heisenberg and Knaut labs for transgenic fish. Diagrams on the right in the graphical abstract were created using BioRender. This work was supported by NIH R01DC015478 and NIH R01GM107733 to S.G.M. A.M. was supported by Human Frontiers Science Program LTF and NIH K99HD098918. A.M. T.J.M. and S.G.M. conceived the project and designed the experiments. A.M. did all of the experiments and analysis. E.H. developed the theoretical model. T.Y.-C.T. made the DN E-cadherin construct. A.M. T.J.M. and S.G.M. wrote the manuscript. All authors edited the manuscript. The authors declare no competing interests. Funding Information: We thank Ian Swinburne, Sandy Nandagopal, and Toru Kawanishi for support, discussions, and reagents. We thank Vanessa Barone, Joseph Nasser, and members of the Megason lab for useful comments on the manuscript and general feedback. We are grateful to the Heisenberg and Knaut labs for transgenic fish. Diagrams on the right in the graphical abstract were created using BioRender. This work was supported by NIH R01DC015478 and NIH R01GM107733 to S.G.M. A.M. was supported by Human Frontiers Science Program LTF and NIH K99HD098918 . Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = dec,
day = "22",
doi = "10.1016/j.cell.2021.11.025",
language = "English",
volume = "184",
pages = "6313--6325.e18",
journal = "Cell",
issn = "0092-8674",
number = "26",
}